Abstract

1. Purpose

Human clinical research has determined that changes in gait speed can be predictive of other impairments and can help identify at-risk individuals for further declines. However, age-related gait changes are not well defined in rodents, even though they are used as the primary pre-clinical model for a multitudes of diseases and for aging research. The purpose of our study was to measure age-related differences in gait, using an automated system, the CatWalk™ XT. Furthermore, age-related functional declines have been associated with a decrease in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Using a model of chronic glutathione deficiency, we sought to determine whether redox state was a key factor in age-related gait impairments. Our hypothesis was that gait declines observed with aging would be exacerbated in glutathione-depleted mice.

2. Methods

Groups of wild-type (gclm+/+) and knock-out (gclm-/-) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements were recorded. Resulting dependent measures including gait speed, front and hind base of support, front and hind stride length, front and hind stride speed, front and hind step cycle, and front and hind duty cycle were analyzed using two-way analyses of variance with Age and Genotype as between-groups factors, followed by pairwise comparisons.

3. Results

Age-related declines were observed in all aforementioned measures of gait, and chronic glutathione depletion was unexpectedly associated with delays in age-related declines for some of the measures.

4. Conclusions

The CatWalk is a useful and sensitive tool to assess gait changes with age in rodents, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion.

ResearchArea

Neuroscience

Presentation Type

Oral presentation

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Research Area

Neuroscience

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Life on the Catwalk – Age and redox state effects on mouse gait

1. Purpose

Human clinical research has determined that changes in gait speed can be predictive of other impairments and can help identify at-risk individuals for further declines. However, age-related gait changes are not well defined in rodents, even though they are used as the primary pre-clinical model for a multitudes of diseases and for aging research. The purpose of our study was to measure age-related differences in gait, using an automated system, the CatWalk™ XT. Furthermore, age-related functional declines have been associated with a decrease in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Using a model of chronic glutathione deficiency, we sought to determine whether redox state was a key factor in age-related gait impairments. Our hypothesis was that gait declines observed with aging would be exacerbated in glutathione-depleted mice.

2. Methods

Groups of wild-type (gclm+/+) and knock-out (gclm-/-) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements were recorded. Resulting dependent measures including gait speed, front and hind base of support, front and hind stride length, front and hind stride speed, front and hind step cycle, and front and hind duty cycle were analyzed using two-way analyses of variance with Age and Genotype as between-groups factors, followed by pairwise comparisons.

3. Results

Age-related declines were observed in all aforementioned measures of gait, and chronic glutathione depletion was unexpectedly associated with delays in age-related declines for some of the measures.

4. Conclusions

The CatWalk is a useful and sensitive tool to assess gait changes with age in rodents, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion.